Nitro derivatives are important starting products in organic synthesis, in which they are generally used as precursors of amino derivatives. Many aromatic nitro derivatives are commercially available or easily obtainable by nitration of suitable aromatic precursors. Aliphatic nitro derivatives are easily accessible by Michael or Henry reactions.
The reduction of nitro derivatives to amines is typically carried out by catalytic hydrogenation (Chem. Rev. 1996, 96, 2035-2052) or by various other processes, such as sodium borohydride in the presence of a catalyst (Catal. Lett. 2008, 123, 264-268), or hydrazine activated with a suitable catalyst (Adv. Synth. Catal. 2007), metals such as zinc or tin (Tetrahedron Lett. 2003, 44, 7783-7787.C), and also processes that use samarium iodide (J. Org. Chem. 2001, 66, 919-924) and complexes of molybdenum and palladium (Org. Lett. 2005, 7, 5087-5090), to name but a few.
Known catalytic systems suffer from various problems. For example, in the case of organometallic catalysts, the use of precious metals is often required, so they primarily involve a cost problem; moreover, any problems of contamination of the products with metal species and problems of disposal and suitable treatment of wastewater must be considered, as they represent serious obstacles to the use of these catalytic systems, for example in the preparation of organic compounds of potential pharmaceutical interest. In addition, it should be borne in mind that nearly all catalytic systems involve hydrogenation as the reduction process, and consequently require specific equipment.
Alternative processes are based on the use of tin salts, the toxicity of which obviously involves serious problems relating to the wastewater disposal processes and potential pollution of the reaction products.
In the case of the known catalysts, their synthesis is often not immediate and requires a synthesis sequence that can include a number of steps, which means that these molecules are neither cheap nor readily available.
In any event, all the existing processes suffer from a lack of general applicability and chemoselectivity problems towards the functional groups present in the substrate.
There is consequently great interest in identifying new processes of reducing nitro derivatives to amines, in particular for the development of new sustainable methodologies (U. Sharma, P. K. Verma, N. K. V. Kumar, M. Bala, B. Singh, Chem. Eur. J. 2011, 17, 5903) which are also economical; in this context, attention is mainly focusing on reduction processes alternative to hydrogenation, with non-toxic reagents, low environmental impact and no metals, especially by companies interested in synthesising organic molecules, including complex ones, which may be chiral or non-chiral, but are characterised by the presence of a plurality of functional groups, whose handling certainly requires the use of highly chemoselective methodologies.
Silyl hydrides (silanes) are compounds with low toxicity and limited costs that contain a silicon-hydrogen bond. Silane derivatives have been used for the reduction of nitroarenes in reactions that proceed in an incomplete way, with low yields (Zh. Obshch. Khim, 1972, 42, 176-180; Dokl. Akad. Nauk., 1970, 195, 352-355). Triethylsilane combined with the Wilkinson catalyst (RhCl(PPh3)3) has been used for the reduction of aromatic nitro derivatives to aniline (Synth. Comm. 1996, 26, 973-980), while in situ generation of molecular hydrogen by adding triethylsilane to palladium on carbon generates the reduction of nitro groups under neutral conditions (J. Org. Chem., 2007, 72, 6599-6601). Aliphatic nitro derivatives are reduced to the corresponding hydroxylamines with triethylsilane in the presence of Pd(OAc)2 (Org. Lett., 2005, 7, 5087-5090).
Trichlorosilane is a very low-cost reagent which is widely used as a reducing agent for other substrates (M. Benaglia, S. Guizzetti, L. Pignataro, Coord. Chem. Rev. 2008, 252, 492). The use of this reagent in the presence of Lewis bases, as agent for the reduction of the double carbon-nitrogen bond, e.g. of imines and ketoimines, to give the corresponding amino compounds, has been described in the literature (S. Guizzetti, M. Benaglia, Eur. J. Org. Chem., 2010, 5529-5541). The use of trichlorosilane for the reduction of nitro derivatives is not known.